Background and objective: It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages.
Methods: We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters.
Results: (1) The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P<0.05). The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P<0.05). The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P<0.05). The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P<0.05). (2) The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P<0.05), but not to age, gross type, histological type and lymph node metastasis (P>0.05). The positive rate of CTLA-4 was closely related to age and differentiation (P<0.05), but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P>0.05). CD8 expression was related to clinical stage (P<0.05), but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P>0.05). The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3) There was positive correlation between gp96 and CTLA-4; there was negative correlation between gp96 and CD8, and there was negative correlation between CD8 and CTLA-4 (P<0.05).
Conclusion: Gene expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.
背景与目的: 近年来研究显示gp96在机体发挥抗肿瘤的特异性细胞毒免疫应答中发挥重要作用。本研究旨在探讨热休克蛋白gp96与免疫相关基因CTLA-4、CD8在不同进展阶段肺癌中的表达及生物学意义。
方法: 应用免疫组化Envision法及组织芯片技术检测89例原发肺癌、12例癌前病变、10例正常肺组织及12例淋巴结转移性肺癌中gp96、CTLA-4、CD8的表达，并分析其与肺癌临床病理指标的关系。
结果: ① 原发性肺癌组gp96的阳性率高于正常组与癌前病变组（P < 0.05）。原发性肺癌组和癌前病变组CTLA-4的阳性率均高于正常组（P < 0.05）。CD8在原发性肺癌组的阳性率高于正常组（P < 0.05）。CD8阳性淋巴细胞高表达组gp96阳性率低于低表达组（P < 0.05）。②gp96表达与患者的性别、分化程度和临床分期有关（P < 0.05），而与年龄、肉眼类型、组织学分型和有无淋巴结转移无关（P > 0.05）。CTLA-4表达与年龄、分化程度有关（P < 0.05），而与性别、肉眼类型、组织学分型、临床分期和有无淋巴结转移无关（P > 0.05）。CD8表达与临床分期有关（P < 0.05），而与性别、年龄、肉眼类型、组织学分型、分化程度和有无淋巴结转移无关（P > 0.05）。在鳞癌和小细胞癌中，gp96、CTLA-4的表达阳性率均高于CD8的表达（P < 0.05）。③Gp96与CTLA-4表达呈正相关（P < 0.05），与CD8表达呈负相关（P < 0.05），CD8与CTLA-4表达呈负相关（P < 0.05）。
结论: 在肺癌中gp96的表达与CTLA-4、CD8密切相关，提示三者在肺癌的发生发展中起重要作用，可作为评估患者病情和估计预后的参考指标。